title: Integrative prognostic risk score in acute myeloid leukemia with normal karyotype.
abstract: To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.
authors.affiliation: Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. damm.frederik@mh-hannover.de
authors.forename: Frederik
authors.initials: F
authors.lastname: Damm
authors.forename: Michael
authors.initials: M
authors.lastname: Heuser
authors.forename: Michael
authors.initials: M
authors.lastname: Morgan
authors.forename: Katharina
authors.initials: K
authors.lastname: Wagner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Görlich
authors.forename: Anika
authors.initials: A
authors.lastname: Grosshennig
authors.forename: Iyas
authors.initials: I
authors.lastname: Hamwi
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Ewa
authors.initials: E
authors.lastname: Surdziel
authors.forename: Walter
authors.initials: W
authors.lastname: Fiedler
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Christoph
authors.initials: C
authors.lastname: Reuter
authors.forename: Gerhard
authors.initials: G
authors.lastname: Heil
authors.forename: Ruud
authors.initials: R
authors.lastname: Delwel
authors.forename: Bob
authors.initials: B
authors.lastname: Löwenberg
authors.forename: Peter J M
authors.initials: PJ
authors.lastname: Valk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Krauter
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D000090243:Nucleophosmin; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D000090243:Nucleophosmin